The long-range purpose of this project is to initially study the immunologic aspects of the factor VIII/von Willebrand factor protein and then to study the biochemistry and structure of this protein in man. The topics of present interest are: (1) the defect of the factor VIII/von Willebrand factor protein in hemophilia A, (2) the defect of the factor VIII/von Willebrand factor protein in von Willebrand's disease, (3) the importance of carbohydrate content in biological function, (4) the relationship of carbohydrate content to atherosclerosis, (5) the mechanism of thrombin activation, and (6) biochemical characterization of the biologically active sites of the factor VIII/von Willebrand factor protein.